Project description:Schizophrenia is a complex mental disorder. Accurate diagnosis and classification of schizophrenia has always been a major challenge in clinic due to the lack of biomarkers. Therefore, identifying molecular biomarkers, particularly in the peripheral blood, is of great significance. This study aimed to identify immune-related molecular biomarkers of schizophrenia in peripheral blood. Eighty-four Peripheral blood leukocytes of first-episode drug-naïve (FEDN) patients with schizophrenia and 97 healthy controls were collected and examined using high-throughput RNA-sequencing. Differentially-expressed genes (DEGs) were analysed. Weighted correlation network analysis (WGCNA) was employed to identify schizophrenia-associated module genes. The CIBERSORT algorithm was adopted to analyse immune cell proportions. Then, machine-learning algorithms including random forest, LASSO, and SVM-RFE were employed to screen immune-related predictive genes of schizophrenia. The RNA-seq analyses revealed 734 DEGs. Further machine-learning-based bioinformatic analyses screened out three immune-related predictive genes of schizophrenia (FOSB, NUP43, and H3C1), all of which were correlated with neutrophils and natural killer cells resting.
Project description:Genome-wide patterns of DNA methylation were quantified using the Illumina Infinium HumanMethylation450K BeadChip (“450K array”) in DNA samples isolated from blood for schizophrenia cases, first episode psychosis patients and controls. These samples were profiled as part of a wider study where they were meta-analysed with other cohorts.
Project description:ObjectiveFunctional impairment continues to represent a major challenge in schizophrenia. Surprisingly, patients with schizophrenia report a level of happiness comparable with control subjects, even in the face of the prominent functional deficits, a finding at odds with evidence indicating a positive relation between happiness and level of functioning. In attempting to reconcile these findings, we chose to examine the issue of values, defined as affectively infused criteria or motivational goals used to select and justify actions, people, and the self, as values are related to both happiness and functioning.MethodsFifty-six first-episode patients in remission and 56 healthy control subjects completed happiness and values measures. Statistical analyses included correlations, analysis of variance, structural equation modelling, and smallest space analysis.ResultsResults indicated that patients with schizophrenia placed significantly greater priority on the value dimensions of Tradition (P = 0.02) and Power (P = 0.03), and significantly less priority on Self-direction (P = 0.007) and Stimulation, (P = 0.008).ConclusionsEssentially, people with schizophrenia place more emphasis on the customs and ideas that traditional culture or religion provide in conjunction with a decreased interest in change, which is at odds with the expectations of early adulthood. This value difference could be related to functional deficits. To this point, we have assumed that people hold to the same values that guided them before the illness' onset, but this may not be the case. Our study indicates that values differ in people with schizophrenia, compared with control subjects, even early in the illness and in the face of symptomatic remission.
Project description:BackgroundDecreased P300 amplitude is one of the most consistent findings in patients with schizophrenia. However, whether prolonged P300 latency occurs in patients with schizophrenia, especially first-episode schizophrenia (FES) patients, remains controversial.MethodsA meta-analyses of P300 aberration in FES patients and healthy control(HC) group was conducted. The meta-regression analysis was performed using a random effects model. The pooled standardized effect size (PSES) was calculated as the division of the difference between the means of the two groups by the common standard deviation.ResultsA total of 569 FES patients and 747 HCs were included in this meta-analysis. P300 amplitude was significantly reduced (PSES = -0.83, 95% CI: -1.02-0.65, P = 0.00001) and P300 latency was delayed significantly in FES patients (PSES = -0.48, 95% CI: 0.14-0.81, P = 0.005). The meta-regression analysis showed that task difficulty was a source of heterogeneity.ConclusionsThe meta-analysis confirms that disrupted information processing is found in FES patients, which is manifested by smaller P300 amplitude and delayed P300 latency.
Project description:To explore the genomic architecture of schizophrenia symptomatology, we analysed blood co-expression modules, i.e. clusters of genes with highly correlated expression, in a cohort of remitted first-episode schizophrenia patients with less than 5 years of evolution, and their association with clinical data, including global functioning, clinical symptomatology and premorbid adjustment.
Project description:Blood methylomes of the first-episode schizophrenia patients differing in their response to amisulpride treatment (OPTiMiSE cohort)
Project description:Cerebellar functional dysconnectivity has long been implicated in schizophrenia. However, the detailed dysconnectivity pattern and its underlying biological mechanisms have not been well-charted. This study aimed to conduct an in-depth characterization of cerebellar dysconnectivity maps in early schizophrenia. Resting-state fMRI data were processed from 196 drug-naïve patients with first-episode schizophrenia and 167 demographically matched healthy controls. The cerebellum was parcellated into nine functional systems based on a state-of-the-art atlas, and seed-based connectivity for each cerebellar system was examined. The observed connectivity alterations were further associated with schizophrenia risk gene expressions using data from the Allen Human Brain Atlas. Overall, we observed significantly increased cerebellar connectivity with the sensorimotor cortex, default-mode regions, ventral part of visual cortex, insula, and striatum. In contrast, decreased connectivity was shown chiefly within the cerebellum, and between the cerebellum and the lateral prefrontal cortex, temporal lobe, and dorsal visual areas. Such dysconnectivity pattern was statistically similar across seeds, with no significant group by seed interactions identified. Moreover, connectivity strengths of hypoconnected but not hyperconnected regions were significantly correlated with schizophrenia risk gene expressions, suggesting potential genetic underpinnings for the observed hypoconnectivity. These findings suggest a common bidirectional dysconnectivity pattern across different cerebellar subsystems, and imply that such bidirectional alterations may relate to different biological mechanisms.
Project description:Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P = .012, uncorrected), with rich club connection strength (P = .032, uncorrected) and SC-FC coupling (P < .001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder.
Project description:Emerging evidence has indicated disrupted learned irrelevance (LIrr), a form of selective attention deficit that may contribute to psychotic symptom formation, in schizophrenia. However, previous research mostly focused on chronic patients. There is a paucity of studies on LIrr in first-episode schizophrenia-spectrum disorder (i.e., schizophrenia and schizophreniform disorder; FES), which were limited by small sample size and have produced mixed results. The current study examined a LIrr effect and its relationship with positive symptom severity in 40 briefly-medicated FES patients and 42 demographically-matched healthy controls using a well-validated computerized LIrr paradigm which has been applied in chronic schizophrenia sample. Positive symptoms were assessed by Positive and Negative Syndrome Scale (PANSS) and Psychotic Symptom Rating Scales (PSYRATS). Our results showed that controls demonstrated intact LIrr, with significantly faster learning about previously predictive (relevant) than previously non-predictive (irrelevant) cues. Lack of such normal attention bias towards predictive over non-predictive cues was observed in FES patients, indicating their failure to distinguish between relevant and irrelevant stimuli. Nonetheless, we failed to reveal any significant correlations between learning scores, in particular learning scores for non-predictive cues, and positive symptom measures in FES patients. Learning scores were also not associated with other symptom dimensions, cognitive functions and antipsychotic dose. In conclusion, our findings indicate aberrant LIrr with impaired allocation of attention to relevant versus irrelevant stimuli in briefly-medicated FES patients. Further prospective research is warranted to clarify the longitudinal trajectory of such selective attention deficit and its association with positive symptoms and treatment response in the early course of illness.